Sleep and circadian rhythm alterations in myalgic encephalomyelitis/chronic fatigue syndrome and post-COVID fatigue syndrome and its association with cardiovascular risk factors: A prospective cohort study

Abstract:

This study aimed to investigate circadian rhythm manifestations in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) patients (including a subpopulation of long-COVID patients) and matched healthy controls while also exploring their association with cardiovascular health variables.

Thirty-one ME/CFS patients (75% females), 23 individuals diagnosed with post-COVID ME/CFS (56% females) and 31 matched healthy controls (68% females) were enrolled in this study. Demographic and clinical characteristics were assessed using validated self-reported outcome measures. Actigraphy data, collected over one week, were used to analyze the 24-h profiles of wrist temperature, motor activity, and sleep circadian variables in the study participants. Associations between lipid profile with endothelial dysfunction biomarkers (such as endothelin-1, ICAM-1 and VCAM-1) and with sleep and circadian variables were also studied.

No differences were found in these variables between the two group of patients. Patients showed lower activity and worse sleep quality than matched healthy controls, together with a worse lipid profile than controls, that was associated with disturbances in the circadian temperature rhythm. ICAM-1 levels were associated with plasma lipids in healthy controls, but not in patients, who showed higher levels of endothelin-1 and VCAM-1.

These findings suggest that lipid profiles in ME/CFS are linked to disrupted circadian rhythms and sleep patterns, likely due to endothelial dysfunction. Furthermore, they highlight the intricate relationship between sleep, circadian rhythms, and cardiovascular health in this condition.

Source: Zerón-Rugerio MF, Zaragozá MC, Domingo JC, Sanmartín-Sentañes R, Alegre-Martin J, Castro-Marrero J, Cambras T. Sleep and circadian rhythm alterations in myalgic encephalomyelitis/chronic fatigue syndrome and post-COVID fatigue syndrome and its association with cardiovascular risk factors: A prospective cohort study. Chronobiol Int. 2024 Jul 22:1-12. doi: 10.1080/07420528.2024.2380020. Epub ahead of print. PMID: 39037125. https://pubmed.ncbi.nlm.nih.gov/39037125/

Impaired Sleep in Patients with Post-COVID-19 Syndrome Compared to Healthy Controls: A Cross-Sectional Trial

Abstract:

Introduction: To objectify self-reported sleep disorders in individuals with post-COVID-syndrome (PCS), we aimed to investigate the prevalence and nature of sleep disturbances by polysomnography (PSG) in PCS compared to healthy individuals.

Methods: People with PCS (n = 21) and healthy controls (CON, n = 10) were included in this prospective trial. At baseline, clinical and social anamnesis, lung function, 1 min sit-to-stand test (STST) and Pittsburgh Sleep Quality Index (PSQI) were assessed. For a single-night, sleep health was evaluated by video-PSG. The apnoea/hypopnea index (AHI) was used as the primary outcome.

Results: Twenty patients with PCS (50 ± 11 y, BMI 27.1 m2/kg, SARS-CoV-2 infection 8.5 ± 4.5 months ago) and 10 CON participants (46 ± 10 y, BMI 23.0 m2/kg, no SARS-CoV-2 infection in the history) completed the study. Forced vital capacity (p = 0.018), STST repetitions (p < 0.001), and symptoms of dyspnoea (at rest: p = 0.002, exertion: p < 0.001) were worse in PCS compared to CON. PSQI score (PCS: 7.5 ± 4.7 points) was higher in PCS compared to CON (Δ = 3.7 points, 95% CI [0.4-7.1] p = 0.015), indicating poor sleep in 80% of patients with PCS. Although PSG showed comparable sleep stage distributions in both groups, AHI (Δ = 9.0 n/h, 95% CI [3.3-14.8], p = 0.002), PLM index (Δ = 5.1 n/h, 95% CI [0.4-9.8], p = 0.017), and the prevalence of sleep apnoea (60% vs. 10%, p = 0.028) was significantly higher in PCS compared to CON.

Conclusion: Quantifiable subjective limitations of sleep have been revealed by PSG data in this PCS cohort. More than half of PCS patients had signs of sleep apnoea, highlighting the importance of sleep screening in PCS.

Source: Jarosch I, Schneeberger T, Stegemann A, Gloeckl R, Leitl D, Dennis C, Hitzl W, Schoen C, Koczulla AR. Impaired Sleep in Patients with Post-COVID-19 Syndrome Compared to Healthy Controls: A Cross-Sectional Trial. Respiration. 2024 Mar 1:1-5. doi: 10.1159/000536272. Epub ahead of print. PMID: 38432219. https://karger.com/res/article/doi/10.1159/000536272/896169/Impaired-Sleep-in-Patients-with-Post-COVID-19 (Full text)

The effect of comorbid medical diagnoses on disturbed sleep in chronic fatigue syndrome

Abstract:

Background: Chronic fatigue syndrome [CFS] may occur alone or with fibromyalgia. This has led some to believe the two occur along a common illness spectrum. Evaluating whether this is the case is important as differences in burden or severity of CFS with fibromyalgia (FM) would suggest different underlying pathophysiological processes.

Objective: To determine if Insomnia Severity Index [ISI] scores differ between patients with CFS and those with CFS plus FM. In addition, we aim to determine if insomnia severity is impacted by other comorbid medically unexplained diagnoses.

Methods: 247 patients with CFS completed the ISI and the Centers for Epidemiological Study – Depression. Patient groups were stratified on CFS severity and the presence of FM. A secondary analysis was conducted to evaluate insomnia severity related to the number of comorbid medically unexplained diagnoses including, FM, multiple chemical sensitivity and/or irritable bowel syndrome.

Results: When controlling for depressed mood, ISI did not differ significantly across patient groups defined by CFS severity and FM status. However, independent of mood, ISI was sensitive to multiple diagnoses showing a significant increasing trend from CFS alone to CFS plus one, two or three comorbid diagnoses.

Conclusion: Although CFS severity and FM status do not impact insomnia severity, increased illness burden as manifested by multiple medically unexplained diagnoses does appear to influence insomnia. In contrast to our earlier studies, this study did not find that a comorbid diagnosis of FM in patients with CFS is related to a worse outcome in the variable of interest.

Source: Aaron J. StegnerMichelle Blate & Benjamin H. Natelson (2024) The effect of comorbid medical diagnoses on disturbed sleep in chronic fatigue syndrome, Fatigue: Biomedicine, Health & Behavior, DOI: 10.1080/21641846.2024.2322915 https://www.tandfonline.com/doi/full/10.1080/21641846.2024.2322915

The Head-Up Tilt Table Test as a Measure of Autonomic Functioning among Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Abstract:

Individuals with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) often experience autonomic symptoms. In the present study, we evaluated 193 adults seeking treatment for ME/CFS, who were recruited from an outpatient clinic. The participants completed a head-up tilt table test to assess two common types of orthostatic intolerance, namely, postural orthostatic tachycardia syndrome (POTS) and orthostatic hypotension (OH).
During the tilt test, 32.5% of the participants demonstrated POTS or OH. The participants with either of these two common types of orthostatic intolerance were found to have more problems with sleep and post-exertional malaise as assessed by the DePaul Symptom Questionnaire; these patients also reported more physical and health function limitations. The implications of the findings are discussed.
Source: Jason LA, McGarrigle WJ, Vermeulen RCW. The Head-Up Tilt Table Test as a Measure of Autonomic Functioning among Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Journal of Personalized Medicine. 2024; 14(3):238. https://doi.org/10.3390/jpm14030238 https://www.mdpi.com/2075-4426/14/3/238 (Full text)

Sleep Issues Amongst People With ME – A Conversation with Professor Dorothy Bruck

by Bronc

Just before Xmas 2010 I was overcome by a bout of Swine Flu. After the holiday, which was a complete blur due to sickness, I went back to work in January feeling very weak. Over the course of the next 8 months, up until my diagnosis of ME, I was afflicted by a bewildering variety of symptoms which caused a great deal of physical and mental suffering. The symptoms which affected me the most in some respects were the unrefreshing sleep and acute insomnia which made me fear that I would lose my job. I was working over 50 hours a week in a very stressful and physically demanding job which I increasingly struggled to keep onto partly due to the lack of sleep/unrefreshing sleep. I noticed a considerable decline in my ability to do some of the basics of my job as I struggled to concentrate and felt increasingly unable to keep up with the very demanding target driven regime at work. Trying to teach a class of 30 teenagers can be hard work at the best of times but when you’re getting 4 hours of unrefreshing sleep it can be a nightmare. Once I received my diagnosis of ME one of the first things I asked my GP for was a course of sleeping tablets to help me overcome the worst of the insomnia.

Since my diagnosis unrefreshing sleep and insomnia have been my constant companions. Sadly, none of the health professionals and scientists I’ve spoken to over the years have been able to offer much insight as to what is causing this and what might help treat it.

There is lack of research into this important aspect of ME. As we all know sleep is the foundation stone of good health for anyone. Those of us who live with dysfunctional sleep all the time it can be very debilitating and have a considerable knock on effect on the other symptoms of our illness.

I recently spoke with Professor Dorothy Bruck about her insights into some of the sleep issues which affect people with ME.

Emeritus Professor Bruck’s main area of research interest and expertise is sleep and sleep health. She has been thinking about, and working with, many aspects of sleep for about 40 years. Professor Bruck has had a long academic career at Victoria University in Melbourne, with particular expertise in sleep/wake behaviour, mental health, chronic fatigue syndrome, waking thresholds and human behaviour in emergencies. She has an international research reputation, with over 120 peer-reviewed full-length publications, $2.5 million in competitive grant income, dozens of invited international and national professional speaking engagements, and numerous awards. Professor Bruck’s research has been regularly featured in the media, including Time Magazine and New Scientist. Apart from her academic work Professor Bruck has worked as a sleep psychologist and most recently she was Chair of the Sleep Health Foundation (Australia). She is now semi-retired and lives in the Far South of Tasmania, Australia.

Q1. How did you get involved in the field of M.E. research?

I have been a sleep researcher since undertaking my Honours degree in 1978, with a particular interest in disorders of excessive daytime sleepiness such as narcolepsy.  In 2010 my teenage son was diagnosed with ME/CFS, which left him bed and recliner bound for about 10 of the next 15 years. Remarkably he has now improved sufficiently to hold a job with flexible hours.  While he was very sick I met ME/CFS clinicians and researchers in Melbourne and we managed to obtain funding for a series of studies focussing on sleep and gut microbes.  We have since published this research with Melinda Jackson and Amy Wallis as the first authors.

Q2. In October 2021 the National Institute for Clinical Excellence in the UK issued a new guideline for the treatment and care of people with M.E. This guideline recognised that for a diagnosis of M.E. to be made people had to suffer from four key symptoms. Unrefreshing sleep or non-restorative sleep is recognised as one of the core symptoms of the illness. The sleep disturbance experienced by pwME can be broken down into two categories: disturbed sleep patterns and unrefreshing sleep. Despite this, there is remarkably little research being conducted into this core symptom of the illness. Amongst the limited studies that have been done into this issue there appears to be no consensus as to what is causing the sleep dysfunction among pwME. How would you explain the sleep dysfunction experienced by pwME?

I think the dichotomy between disturbed sleep patterns and unrefreshing sleep is quite useful, keeping in mind however, that a pwME/CFS may have both.  Neither are unique to ME/CFS.

Disturbed sleep patterns (where the person is unable to sleep when they want to) may arise from co-morbidities with ME/CFS, such as sleep apnea, insomnia and circadian rhythm disorders. Sometimes the latter two disorders may begin with, or be perpetuated by, behavioural changes in sleep/wake behaviours that lead to disturbed sleep.

  • For example, the fatigue associated with ME/CFS may lead to irregular sleep patterns where the person sleeps episodically (i.e. naps) across the 24 hour period and the circadian (24 hour) rhythm becomes confused. The person’s sleep quality suffers because they are no longer getting their main sleep period in a single block at the time the body clock expects it. A different pattern that we may see in ME./CFS is Delayed Sleep Phase Disorder, where the person is very much an ‘evening’ type, going to bed late and getting up late. People who get insufficient outdoor light during the daytime are particularly susceptible to this.  Sometimes their body clock begins to ‘free run’ and each night they may go to bed later than the previous night, so their ‘day’ may be 25 hours instead of 24 hours.
  • Behavioural changes that may precipitate insomnia include decreased sleep drive (or sleep pressure) arising from reduced activity, significant napping during the day, reduced exposure to daytime light, worry at night about the consequences of having ME/CFS, and/or longer time in bed trying to sleep than the actual sleep duration that person may need. For example, due to boredom and/or feelings of fatigue, turning lights off from 9pm to 8am each night (i.e. 11 hours trying to sleep) when the person may only need 8 hours of actual sleep.  Best if lights-out time equals sleep time required.  The research shows quite clearly that treatment with Cognitive Behavioural Therapy for Insomnia can provide significant improvements in people whose sleep has been impaired by such behavioural factors and online programs are available.

On the other hand, disturbed sleep patterns in pwME/CFS may arise, not from behavioural factors, but from factors associated with ME/CFS itself, such as impaired melatonin secretion or other imbalances in the many hormonal or metabolic or neurological factors that we are only now beginning to understand affect sleep patterns.  Such imbalances may, in fact lead to either disturbed sleep patterns or unrefreshing sleep.

Unrefreshing sleep occurs across the population, both in people with a range of clinical conditions and sometimes in people with no diagnosed medical problem.  It is usually described by self-report. It is likely to be a very heterogenous phenomenon. A study by El-Mekkawy Leqaa et al (2022) noted a significant change in delta wave power (deep sleep) in the temporal brain region in those with unrefreshing sleep arising from sleep apnea, compared to controls. In our review of sleep patterns in ME/CFS (Jackson and Bruck, 2012) we concluded that technological advances in the assessment/monitoring of sleep may lead to further understanding of how the micro-structure of sleep may differ between those with self-reported unrefreshing sleep compared to quality sleep.

Q3. Anecdotal evidence from some pwME and a few research studies suggest that the sleep disturbance that people experience can have a significant impact on their cognitive abilities. How prevalent is this? What may be causing the sleep disturbance to impact people’s cognitive function?

Any ongoing sleep disturbance will affect a person’s cognitive abilities. Attention, concentration, memory and reaction time may all be affected in some way depending on (a) their overall health (physical and/or mental) and (b) individual differences in how poor sleep quality affects an individual.  It seems reasonable to think that a pwME/CFS that includes the symptom of brain fog would be affected by the cognitive impairments we associate with poor sleep in an additive way.

Q.4 Is there any evidence that non-restorative sleep is impacting other symptoms which pwME experience such as pain?

I believe that ANY ongoing poor quality sleep, whether it is unrestorative sleep or disturbed sleep will affect a range of ME/CFS symptoms, possibly all.  Pain and brain fog are likely to be particularly affected.

With regard to pain we know that sleep loss increases the experience of pain.  Krause et al (2019) showed that acute sleep deprivation amplifies pain reactivity within the human primary somatosensory cortex, lowers pain thresholds and that ‘even modest nightly changes in sleep quality within an individual determine consequential day-to-day changes in experienced pain’.

Q5. Having a clearer understanding about the pathophysiology of non-restorative sleep in pwME may lead to better treatment options for patients. Are you aware of any clinical trials which are exploring treatment issues for non-restorative sleep in pwME?

Unfortunately not.

Q6. Many people with M.E. report that there is a direct link between the degree of their non-restorative sleep and the depth of the fatigue they experience the next day. What research has been done into this particular issue and what were their findings?

To my knowledge this issue has not yet been investigated in pwME/CFS.  However, cognitive fatigue as measured on a range of working memory tests (Benkirane et al, 2022) found that the main effect of sleep fragmentation was to increase subjectively reported fatigue rather than reduce cognitive test performance.  This study, using healthy participants, highlights the difficulties in objectively measuring fatigue, as many people can rally their mental resources for short-term testing in a research setting.  This may have little to do with how fatigue is experienced in real-life settings.

Q7. What further research is required to investigate the causes of non-restorative sleep and the impact this has on cognitive function, fatigue and pain in pwME?

There are so many unanswered questions.  The first step for any such research is to have a standard definition of non-restorative sleep.  Is it a certain level of sleep fragmentation? Sleep disruption? Lower EEG delta power? Subjective report in the light of an otherwise normal sleep diary?  Is reported non-restorative sleep the same for someone with sleep apnea, vivid dreaming or ME/CFS?

Impact of sleep disruption on cognitive function in patients with post-acute sequelae of SARS-CoV-2 infection: Initial findings from a Neuro-COVID-19 clinic

Abstract:

Introduction: Fatigue, brain fog and sleep disturbance are among the most common symptoms of post-acute sequelae of SARS-CoV-2 infection (PASC). We sought to determine the impact of sleep disruption on cognition and quality-of-life in patients with neurologic manifestations of PASC (Neuro-PASC).

Methods: Thirty-nine patients were recruited from Neuro-COVID-19 clinic. Mean age was 48.1 years, 71.8% were female, and 82% were never hospitalized for COVID-19. Patients were evaluated via clinical assessment, quality-of-life measures in domains of cognitive function, fatigue, sleep disturbance, anxiety, and depression, NIH toolbox cognitive tests, and 7 days of wrist actigraphy.

Results: The median number of neurologic symptoms attributed to PASC was 6, with brain fog being the most common in 89.7%. Regarding non-neurologic symptoms, 94.9% complained of fatigue and 74.4% of insomnia. Patients reported significant impairment in all quality-of-life domains and performed worse in a task of attention compared to a normative US population. Actigraphy showed Neuro-PASC patients had lower sleep efficiency, longer sleep latency (both p<0.001) and later sleep midpoint (p=0.039) compared to 71 age-matched healthy controls with no PASC history. Self-reported cognitive symptoms correlated with severity of fatigue (p<0.001), anxiety (p=0.05), and depression (p<0.01). Objective evidence of sleep disruption measured by wakefulness after sleep onset, sleep efficiency and latency were associated with decreased performance in attention and processing speed.

Conclusion: Prospective studies including larger populations of patients are needed to fully determine the interplay of sleep disruption on the cognitive function and quality of life of patients with PASC.

Source: Kathryn J Reid, Louis T Ingram, Millenia Jimenez, Zachary S Orban, Sabra M Abbott, Daniela Grimaldi, Kristen L Knutson, Phyllis C Zee, Igor J Koralnik, Mathew B Maas, Impact of sleep disruption on cognitive function in patients with post-acute sequelae of SARS-CoV-2 infection: Initial findings from a Neuro-COVID-19 clinic, SLEEP Advances, 2024;, zpae002, https://doi.org/10.1093/sleepadvances/zpae002 https://academic.oup.com/sleepadvances/advance-article/doi/10.1093/sleepadvances/zpae002/7517273 (Full text available as PDF file)

Insomnia and sleep characteristics in post COVID-19 fatigue: A cross-sectional case-controlled study

Abstract:

Objective: Following COVID-19 many patients report persistent fatigue and insomnia. Given the overlapping features, insomnia can be underdiagnosed in post-COVID-19 fatigue patients. This study aimed to determine insomnia severity, prevalence of clinical insomnia and sleep characteristics of post-COVID-19 fatigue patients. Data of post-COVID-19 fatigue patients were compared with those of patients with chronic fatigue syndrome (ME/CFS), a condition resembling post-COVID-19 fatigue.

Methods: In this cross-sectional case-controlled study, insomnia severity, assessed with the Insomnia Severity Index (ISI), and prevalence of clinical insomnia (ISI score ≥ 10), were determined in patients with post-COVID-19 fatigue (n = 114) and compared with ME/CFS (n = 59) using ANCOVA and logistic regression, respectively. Linear regression analyses were used to evaluate whether mood, concentration problems, pain, fatigue (assessed with questionnaires) and diagnosis were associated with insomnia. Sleep characteristics were determined with a sleep diary and accelerometer in post-COVID-19 fatigue and compared with ME/CFS using ANCOVA.

Results: In patients with post-COVID-19 fatigue mean (SD) insomnia severity was 11.46 (5.7) and 64% reported clinical insomnia. Insomnia severity was significantly associated with depressive symptoms (ß = 0.49, p = 0.006) and age (ß = 0.08, p = 0.04). The mean (SD) subjective sleep duration was 7.4 (1.0) hours with a sleep efficiency of 82 (11)%. Several subjective sleep characteristics of the post-COVID-19 fatigue patients differed from ME/CFS patients; only sleep duration, being significantly shorter in post-COVID-19 fatigue patients (p = 0.003), seemed clinically relevant (d = 0.58).

Conclusion: Insomnia severity and prevalence of clinical insomnia are high in patients with post-COVID-19 fatigue. Insomnia should be assessed and if present treated with insomnia focused therapy.

Source: Nynke L. Rauwerda, Tanja A. Kuut, Annemarie M.J. Braamse, Irene Csorba, Pythia Nieuwkerk, Annemieke van Straten, Hans Knoop. Insomnia and sleep characteristics in post COVID-19 fatigue: A cross-sectional case-controlled study. Journal of Psychosomatic Research, 2023, 111522.ISSN 0022-3999, https://doi.org/10.1016/j.jpsychores.2023.111522.https://www.sciencedirect.com/science/article/pii/S0022399923003793

Habitual short sleepers with pre-existing medical conditions are at higher risk of Long COVID

Abstract:

STUDY OBJECTIVES: Preliminary evidence suggests that the risk of Long COVID is higher among people with pre-existing medical conditions. Based on its proven adjuvant role in immunity, habitual sleep duration may alter the risk for developing Long COVID. The objective of this study was to determine whether the odds of Long COVID are higher amongst those with pre-existing medical conditions, and whether the strength of this association varies by habitual sleep duration.

METHODS: Using data from 13,461 respondents from 16 countries who participated in the 2021 survey based International COVID Sleep Study II (ICOSS II), we studied the associations between habitual sleep duration, pre-existing medical conditions, and Long COVID.

RESULTS: Of 2,508 individuals who had COVID-19, 61% reported at least one Long COVID symptom. Multivariable logistic regression analysis showed that the risk of having Long COVID was 1.8-fold higher for average-length sleepers (6-9h/night) with pre-existing medical conditions compared to those without pre-existing medical conditions [aOR 1.84 (1.18-2.90), P=0.008]. The risk of Long COVID was 3-fold higher for short sleepers with pre-existing medical conditions [aOR 2.95 (1.04-8.4), P=0.043] and not significantly higher for long sleepers with pre-existing conditions [aOR 2.11 (0.93-4.77), P=0.073] compared to average-length sleepers without pre-existing conditions.

CONCLUSIONS: Habitual short nighttime sleep duration exacerbated the risk of Long COVID in individuals with pre-existing conditions. Restoring nighttime sleep to average duration represents a potentially modifiable behavioral factor to lower the odds of Long COVID for at-risk patients.

Source: Linor Berezin, MD, et al. Habitual short sleepers with pre-existing medical conditions are at higher risk of Long COVID. Journal of Clinical Sleep Medicine, Articles in Advance. https://jcsm.aasm.org/doi/pdf/10.5664/jcsm.10818 (Full text)

Serum from Myalgic encephalomyelitis/chronic fatigue syndrome patients causes loss of coherence in cellular circadian rhythms

Abstract:

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a disabling disorder characterized by disrupted daily patterns of activity, sleep, and physiology. Past studies in ME/CFS patients have examined circadian rhythms, suggested that desynchronization between central and peripheral rhythms may be an important pathological feature, and identified associated changes in post-inflammatory cytokines such as transforming growth factor beta (TGFB). However, no previous studies have examined circadian rhythms in ME/CFS using cellular models or studied the role of cytokines on circadian rhythms.

In this study, we used serum samples previously collected from ME/CFS patients (n = 20) selected for the presence of insomnia symptoms and matched controls (n = 20) to determine the effects of serum factors and TGFB on circadian rhythms in NIH3T3 mouse immortalized fibroblasts stably transfected with the Per2-luc bioluminescent circadian reporter.

Compared to control serum, ME/CFS serum caused a significant loss of rhythm robustness (decreased goodness of fit) and nominally increased the rate of damping of cellular rhythms. Damping rate was associated with insomnia severity in ME/CFS patients using the Pittsburgh Sleep Quality Index (PSQI). Recombinant TGFB1 peptide applied to cells reduced rhythm amplitude, caused phase delay and decreased robustness of rhythms.

However, there was no difference in TGFB1 levels between ME/CFS and control serum indicating the effects of serum on cellular rhythms cannot be explained by levels of this cytokine. Future studies will be required to identify additional serum factors in ME/CFS patients that alter circadian rhythms in cells.

Source: Heather Wei, Zoe Adelsheim, Rita Fischer, Michael J. McCarthy. Serum from Myalgic encephalomyelitis/chronic fatigue syndrome patients causes loss of coherence in cellular circadian rhythms. Journal of Neuroimmunology. Available online 24 June 2023, 578142. https://doi.org/10.1016/j.jneuroim.2023.578142 https://www.sciencedirect.com/science/article/abs/pii/S0165572823001285

Do Pre-existing Sleep Disorders Worsen Long COVID Fatigue and Brain Fog?

Abstract:

Introduction: Long COVID is common after COVID-19 infection and leads to functional limitations with most reporting substantial symptom burden from fatigue. Symptoms in sleep disorders are attributed to inflammatory dysregulation and may predispose to fatigue expression. We hypothesize prior diagnoses of sleep disorders are associated with severity of long COVID fatigue.
Methods: A retrospective EMR review was performed of 210 consecutive adult patients (9/2021 to 2/2022) referred at least 3 months after COVID-19 infection seen in a new community-based long COVID clinic. The intake process collected demographics, past medical history, functional questionnaires, and symptom checklists. Primary outcome was Fatigue Severity Scale (FSS) score. Sleep disorders were evaluated as a composite of self-reported insomnia, sleep disordered breathing, and restless legs syndrome as well as subset analyses of each disorder. Secondary outcome was physical functioning measured by ECOG performance scale. Linear analyses were used for FSS and ECOG analyses. Adjustors included age, sex, body mass index (BMI), and whether patient had COVID-19 hospitalization.
Results: Cohort was female (66.2%), aged 51.6±SD14.4 yrs, BMI 29.8 [IQR 26.2, 37.7]). Prior chronic insomnia was present in 9%, sleep disordered breathing in 23%, and RLS in 4%; the pooled history of sleep disorders was 30%. Fatigue was reported in 76% with mean FSS score of 5.44 [interquartile range, IQR: 4.11,6.44]; 48% reported brain fog. The interval between acute COVID infection and clinic evaluation was 10.4±5.34 months and had no association to FSS severity (r = 0.07, p = 0.30). Sleep disorders in aggregate, insomnia, and restless legs syndrome had no associations with fatigue or functional status. Sleep disordered breathing had an association to fatigue in unadjusted (β = 0.68, 95% confidence interval, [CI]:0.13,1.24), but not adjusted models (β = 0.53, 95%CI: -0.06,1.13). Sleep disorders both in aggregate and evaluated individually had no associations to brain fog.
Conclusion: A prior history of sleep disorders contributed little to post-COVID fatigue reported in those presenting to a community-based Long COVID clinic.

Source: Isabelle Carter and others, 0967 Do Pre-existing Sleep Disorders Worsen Long COVID Fatigue and Brain Fog?, Sleep, Volume 46, Issue Supplement_1, May 2023, Pages A426–A427, https://doi.org/10.1093/sleep/zsad077.0967 (Full text is available as PDF file)